Regulation of α2-adrenoceptors in human vascular smooth muscle cells

Maqsood A. Chotani, Srabani Mitra, Baogen Y. Su, Sheila Flavahan, Ali H. Eid, K. Reed Clark, Christine R. Montague, Hervé Paris, Diane E. Handy, Nicholas Flavahan

Research output: Contribution to journalArticle

Abstract

This study analyzed the regulation of α2-adrenoceptors (α2-ARs) in human vascular smooth muscle cells (VSMs). Saphenous veins and dermal arterioles or VSMs cultured from them expressed high levels of α2-ARs (α2C > α 2A, via RNase protection assay) and responded to α 2-AR stimulation [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK-14,304, 1 μM)] with constriction or calcium mobilization. In contrast, VSMs cultured from aorta did not express α2-ARs and neither cultured cells nor intact aorta responded to UK-14,304. Although α2-ARs (α2C ≫ α2A) were detected in aortas, α2C-ARs were localized by immunohistochemistry to VSMs of adventitial arterioles and not aortic media. In contrast with aortas, aortic arterioles constricted in response to α2-AR stimulation. Reporter constructs demonstrated higher activities for α2A- and α2C-AR gene promoters in arteriolar compared with aortic VSMs. In arteriolar VSMs, serum increased expression of α2C-AR mRNA and protein but decreased expression of α2A-ARs. Serum induction of α2C-ARs was reduced by inhibition of p38 mitogen-activated protein kinase (MAPK) with 2 μM SB-202190 or dominant-negative p38 MAPK. UK-14,304 (1 μM) caused calcium mobilization in control and serum-stimulated cells: in control VSMs, the response was inhibited by the α2A-AR antagonist BRL-44408 (100 nM) but not by the α2C-AR antagonist MK-912 (1 nM), whereas after serum stimulation, MK-912 (1 nM) but not BRL-44408 (100 nM) inhibited the response. These results demonstrate site-specific expression of α2-ARs in human VSMs that reflects differential activity of α2-AR gene promoters; namely, high expression and function in venous and arteriolar VSMs but no detectable expression or function in aortic VSMs. We found that α2C-ARs can be dramatically and selectively induced via a p38 MAPK-dependent pathway. Therefore, altered expression of α 2C-ARs may contribute to pathological changes in vascular function.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume286
Issue number1 55-1
StatePublished - Jan 2004
Externally publishedYes

Fingerprint

Vascular Smooth Muscle
Adrenergic Receptors
Smooth Muscle Myocytes
L 657743
Aorta
Arterioles
p38 Mitogen-Activated Protein Kinases
Serum
Calcium
Adventitia
Mitogen-Activated Protein Kinase 1
Saphenous Vein
Ribonucleases
Constriction
Genes
Blood Vessels
Cultured Cells
Immunohistochemistry
Messenger RNA
Skin

Keywords

  • BRL-44408
  • Microcirculation
  • MK-912
  • p38 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Physiology

Cite this

Chotani, M. A., Mitra, S., Su, B. Y., Flavahan, S., Eid, A. H., Clark, K. R., ... Flavahan, N. (2004). Regulation of α2-adrenoceptors in human vascular smooth muscle cells. American Journal of Physiology - Heart and Circulatory Physiology, 286(1 55-1).

Regulation of α2-adrenoceptors in human vascular smooth muscle cells. / Chotani, Maqsood A.; Mitra, Srabani; Su, Baogen Y.; Flavahan, Sheila; Eid, Ali H.; Clark, K. Reed; Montague, Christine R.; Paris, Hervé; Handy, Diane E.; Flavahan, Nicholas.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 286, No. 1 55-1, 01.2004.

Research output: Contribution to journalArticle

Chotani, MA, Mitra, S, Su, BY, Flavahan, S, Eid, AH, Clark, KR, Montague, CR, Paris, H, Handy, DE & Flavahan, N 2004, 'Regulation of α2-adrenoceptors in human vascular smooth muscle cells', American Journal of Physiology - Heart and Circulatory Physiology, vol. 286, no. 1 55-1.
Chotani, Maqsood A. ; Mitra, Srabani ; Su, Baogen Y. ; Flavahan, Sheila ; Eid, Ali H. ; Clark, K. Reed ; Montague, Christine R. ; Paris, Hervé ; Handy, Diane E. ; Flavahan, Nicholas. / Regulation of α2-adrenoceptors in human vascular smooth muscle cells. In: American Journal of Physiology - Heart and Circulatory Physiology. 2004 ; Vol. 286, No. 1 55-1.
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AU - Eid, Ali H.

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